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Lhx8 regulates primordial follicle activation and postnatal folliculogenesis

Ren, Y and Suzuki, H and Jagarlamudi, K and Golnoski, K and McGuire, M and Lopes, R and Pachnis, V and Rajkovic, A (2015) Lhx8 regulates primordial follicle activation and postnatal folliculogenesis. BMC Biology, 13 (1).

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Abstract

© 2015 Ren et al. Background: The early stages of ovarian follicle formation-beginning with the breakdown of germ cell cysts and continuing with the formation of primordial follicles and transition to primary and secondary follicles-are critical in determining reproductive life span and fertility. Previously, we discovered that global knockouts of germ cell-specific transcriptional co-regulators Sohlh1, Sohlh2, Lhx8, and Nobox, cause rapid oocyte loss and ovarian failure. Also factors such as Nobox and Sohlh1 are associated with human premature ovarian failure. In this study, we developed a conditional knockout of Lhx8 to study oocyte-specific pathways in postnatal folliculogenesis. Results: The conditional deficiency of Lhx8 in the oocytes of primordial follicles leads to massive primordial oocyte activation, in part, by indirectly interacting with the PI3K-AKT pathway, as shown by synergistic effects on FOXO3 nucleocytoplasmic translocation and rpS6 activation. However, LHX8 does not directly regulate members of the PI3K-AKT pathway; instead, we show that LHX8 represses Lin28a expression, a known regulator of mammalian metabolism and of the AKT/mTOR pathway. LHX8 can bind to the Lin28a promoter, and the depletion of Lin28a in Lhx8-deficient oocytes partially suppresses primordial oocyte activation. Moreover, unlike the PI3K-AKT pathway, LHX8 is critical beyond primordial follicle activation, and blocks the primary to secondary follicle transition. Conclusions: Our results indicate that the LHX8-LIN28A pathway is essential in the earliest stages of primordial follicle activation, and LHX8 is an important oocyte-specific transcription factor in the ovary for regulating postnatal folliculogenesis.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Ren, Yyur4@pitt.eduYUR4
Suzuki, H
Jagarlamudi, K
Golnoski, K
McGuire, M
Lopes, R
Pachnis, V
Rajkovic, Aalr110@pitt.eduALR110
Centers: Other Centers, Institutes, or Units > Magee-Women's Research Institute
Date: 16 June 2015
Date Type: Publication
Journal or Publication Title: BMC Biology
Volume: 13
Number: 1
DOI or Unique Handle: 10.1186/s12915-015-0151-3
Schools and Programs: Graduate School of Public Health > Human Genetics
School of Medicine > Obstetrics, Gynecology, and Reproductive Sciences
School of Medicine > Pathology
Refereed: Yes
Date Deposited: 17 Aug 2016 13:24
Last Modified: 13 Oct 2017 21:55
URI: http://d-scholarship.pitt.edu/id/eprint/29243

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